Klinik Araştırma
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Genetic polymorphisms and Methotrexate response in patients with rheumatoid arthritis

Yıl 2024, Cilt: 28 Sayı: 4, 1285 - 1292, 28.06.2025

Milka Grk Biljana Jekic Vita Dolzan Nela Maksimovic Tatjana Damnjanovic Milica Rasic Ivana Novakovic Dijana Perovic Jelena Carkic Marija Dusanovic Pjevic

Öz

In the context of rheumatoid arthritis (RA) treatment, Methotrexate (MTX) plays a crucial role in preventing joint damage and bone erosion (BE). RA is characterized by elevated levels of matrix metalloproteinase 2 (MMP2), an enzyme responsible for extracellular matrix degradation, which contributes to joint damage and inflammation. Tissue inhibitor of metalloproteinase 2 (TIMP2) counteracts MMP2, and an imbalance between the two can exacerbate BE. Inosine triphosphatase (ITPA) is an enzyme involved in regulating inosine triphosphate levels, potentially linked to RA susceptibility. Genetic variations in ITPA, MMP2, and TIMP2 genes can influence MTX's efficacy. A study of 122 RA patients on MTX monotherapy assessed its effectiveness using Disease Activity Score (DAS28) changes over 6 months following EULAR response criteria. Genotyping, including MMP2 (rs243866, rs2285053), TIMP2 (rs2277698), and ITPA (rs1127354) polymorphisms, was performed. Among the patients, 87.7% were responders, 63.9% experienced BE, and 24.6% encountered adverse events. Notably, patients with the MMP2 (rs243866) GG genotype were the only ones reporting nausea (p=0.025). Patients with both the MMP2 (rs2285053) CC and TIMP2 (rs2277698) CT genotypes had a lower incidence of BE compared to those lacking this combination (p=0.048). The TIMP2 (rs2277698) CC genotype was associated with a higher baseline DAS28 score (p=0.035). In summary, this study suggests that specific MMP2/TIMP2 genotype combinations may serve as predictors for BE development in RA patients undergoing MTX monotherapy.

Anahtar Kelimeler

Methotrexate MMP2 TIMP2 ITPA rheumatoid arthritis polymorphism

Kaynakça

  • [1] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010; 69(9): 1580-8. https://doi.org/10.1136/ard.2010.138461
  • [2] Schett G, Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol. 2012; 8(11): 656-64. https://doi.org/10.1038/nrrheum.2012.153
  • [3] Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JMW, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poór G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017; 76(6): 960-977. https://doi.org/10.1136/annrheumdis-2016-210715
  • [4] Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, Caporali R, Edwards CJ, Hyrich KL, Pope JE, de Souza S, Stamm TA, Takeuchi T, Verschueren P, Winthrop KL, Balsa A, Bathon JM, Buch MH, Burmester GR, Buttgereit F, Cardiel MH, Chatzidionysiou K, Codreanu C, Cutolo M, den Broeder AA, El Aoufy K, Finckh A, Fonseca JE, Gottenberg JE, Haavardsholm EA, Iagnocco A, Lauper K, Li Z, McInnes IB, Mysler EF, Nash P, Poor G, Ristic GG, Rivellese F, Rubbert-Roth A, Schulze-Koops H, Stoilov N, Strangfeld A, van der Helm-van Mil A, van Duuren E, Vliet Vlieland TPM, Westhovens R, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023; 82(1): 3-18. https://doi.org/10.1136/ard-2022-223356
  • [5] Owen SA, Hider SL, Martin P, Bruce IN, Barton A, Thomson W. Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients. Pharmacogenomics J. 2013; 13(3): 227-34. https://doi.org/10.1038/tpj.2012.7
  • [6] Brown PM, Pratt AG, Isaacs JD. Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nat Rev Rheumatol. 2016; 12(12): 731-742. https://doi.org/10.1038/nrrheum.2016.175
  • [7] Friedman B, Cronstein B. Methotrexate mechanism in treatment of rheumatoid arthritis. Joint Bone Spine. 2019; 86(3): 301-307. https://doi.org/10.1016/j.jbspin.2018.07.004
  • [8] Bierau J, Lindhout M, Bakker JA. Pharmacogenetic significance of inosine triphosphatase. Pharmacogenomics. 2007; 8(9): 1221-8. https://doi.org/10.2217/14622416.8.9.1221
  • [9] Sun R, Huang Y, Zhang H, Liu R. MMP-2, TNF-α and NLRP1 polymorphisms in Chinese patients with ankylosing spondylitis and rheumatoid arthritis. Mol Biol Rep. 2013; 40(11): 6303-8. https://doi.org/10.1007/s11033-013-2743-8
  • [10] Kukkonen MK, Tiili E, Vehmas T, Oksa P, Piirilä P, Hirvonen A. Association of genes of protease-antiprotease balance pathway to lung function and emphysema subtypes. BMC Pulm Med. 2013; 13: 1-10. https://doi.org/10.1186/1471-2466-13-36
  • [11] Mi M, Shi S, Li T, Holz J, Lee YJ, Sheu TJ, Liao Q, Xiao T. TIMP2 deficient mice develop accelerated osteoarthritis via promotion of angiogenesis upon destabilization of the medial meniscus. Biochem Biophys Res Commun. 2012; 423(2): 366-72. https://doi.org/10.1016/j.bbrc.2012.05.132
  • [12] Varani K, Padovan M, Vincenzi F, Targa M, Trotta F, Govoni M, Borea PA. A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res Ther. 2011; 13(6): R197. https://doi.org/10.1186/ar3527
  • [13] Chen Y, Zou K, Sun J, Yang Y, Liu G. Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheumatoid arthritis? A systematic review and meta-analysis. Pharmacogenomics. 2017; 18(2): 175-195. https://doi.org/10.2217/pgs-2016-0158
  • [14] Dervieux T, Wessels JA, van der Straaten T, Penrod N, Moore JH, Guchelaar HJ, Kremer JM. Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis. Pharmacogenet Genomics. 2009; 19(12): 935-44. DOI: 10.1097/FPC.0b013e32833315d1
  • [15] Quaranta S, Thomas F. Pharmacogenetics of anti-cancer drugs: State of the art and implementation–recommendations of the French National Network of Pharmacogenetics. Therapies. 2017; 72(2): 205-15. https://doi.org/10.1016/j.therap.2017.01.005
  • [16] Taylor JC, Bongartz T, Massey J, Mifsud B, Spiliopoulou A, Scott IC, Wang J, Morgan M, Plant D, Colombo M, Orchard P, Twigg S, McInnes IB, Porter D, Freeston JE, Nam JL, Cordell HJ, Isaacs JD, Strathdee JL, Arnett D, de Hair MJH, Tak PP, Aslibekyan S, van Vollenhoven RF, Padyukov L, Bridges SL, Pitzalis C, Cope AP, Verstappen SMM, Emery P, Barnes MR, Agakov F, McKeigue P, Mushiroda T, Kubo M, Weinshilboum R, Barton A, Morgan AW, Barrett JH; MATURA; and PAMERA; Consortia. Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. Pharmacogenomics J. 2018; 18(4): 528-538. https://doi.org/10.1038/s41397-018-0025-5
  • [17] Relling MV, Klein TE, Gammal RS, Whirl-Carrillo M, Hoffman JM, Caudle KE. The Clinical Pharmacogenetics Implementation Consortium: 10 Years Later. Clin Pharmacol Ther. 2020; 107(1): 171-175. https://doi.org/10.1002/cpt.1651
  • [18] Li P, Tao SS, Zhao MQ, Li J, Wang X, Pan HF, Ye DQ. Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to Rheumatoid Arthritis: A Meta-Analysis. Immunol Invest. 2015; 44(7): 603-15. https://doi.org/10.3109/08820139.2015.1056346
  • [19] Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006; 11: 529-43. https://doi.org/10.2741/1817
  • [20] Combe B, Landewe R, Daien CI, Hua C, Aletaha D, Álvaro-Gracia JM, Bakkers M, Brodin N, Burmester GR, Codreanu C, Conway R, Dougados M, Emery P, Ferraccioli G, Fonseca J, Raza K, Silva-Fernández L, Smolen JS, Skingle D, Szekanecz Z, Kvien TK, van der Helm-van Mil A, van Vollenhoven R. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis. 2017; 76(6): 948-959. https://doi.org/10.1136/annrheumdis-2016-210602
  • [21] Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial. Arthritis Rheum. 2008; 58(2 Suppl): S126-35. doi: 10.1002/art.23364. PMID: 18240203. https://doi.org/10.1002/art.23364
  • [22] Itoh T, Matsuda H, Tanioka M, Kuwabara K, Itohara S, Suzuki R. The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis J Immunol. 2002; 169(5): 2643-7. https://doi.org/10.4049/jimmunol.169.5.2643
  • [23] Hussein R, Aboukhamis I. Serum matrix metalloproteinase-3 levels monitor the therapeutic efficacy in Syrian patients with rheumatoid arthritis. Heliyon. 2023; 9(3): e14008. https://doi.org/10.1016/j.heliyon.2023.e14008
  • [24] Sabbatini Sabbatini AR, Barbaro NR, de Faria AP, Ritter AMV, Modolo R, Correa NB, Brunelli V, Pinho C, Fontana V, Moreno H. Matrix metalloproteinase-2 -735C/T polymorphism is associated with resistant hypertension in a specialized outpatient clinic in Brazil. Gene. 2017; 620: 23-29. https://doi.org/10.5935/abc.20150060
  • [25] Burgis NE. A disease spectrum for ITPA variation: advances in biochemical and clinical research. J Biomed Sci. 2016; 23(1): 73. https://doi.org/10.1186/s12929-016-0291-y
  • [26] Wessels JA, Kooloos WM, De Jonge R, De Vries-Bouwstra JK, Allaart CF, Linssen A, Collee G, De Sonnaville P, Lindemans J, Huizinga TW, Guchelaar HJ. Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2006; 54(9): 2830-9. https://doi.org/10.1002/art.22032
  • [27] Lee YC, Cui J, Costenbader KH, Shadick NA, Weinblatt ME, Karlson EW. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford). 2009; 48(6): 613-7. https://doi.org/10.1093/rheumatology/ken513
  • [28] Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Am. 2009;35(4):745-57. Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Am. 2009; 35(4): 745-57. https://doi.org/10.1016/j.rdc.2009.10.001
  • [29] Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3): 315-24. https://doi.org/10.1002/art.1780310302
  • [30] Fransen J, Kooloos WM, Wessels JA, Huizinga TW, Guchelaar HJ, van Riel PL, Barrera P. Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure. Pharmacogenomics. 2012; 13(9): 1087-94. https://doi.org/10.2217/pgs.12.83
  • [31] Vejnović D, Milić V, Popović B, Damnjanović T, Maksimović N, Bunjevački V, Krajinović M, Novaković I, Damjanov N, Jekić B. Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. Expert Opin Drug Metab Toxicol. 2019; 15(3): 253-257. https://doi.org/10.1080/17425255.2019.1563594
  • [32] Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215. https://doi.org/10.1093/nar/16.3.1215
  • [33] Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005; 21(2): 263-5. https://doi.org/10.1093/bioinformatics/bth457

Yıl 2024, Cilt: 28 Sayı: 4, 1285 - 1292, 28.06.2025

Milka Grk Biljana Jekic Vita Dolzan Nela Maksimovic Tatjana Damnjanovic Milica Rasic Ivana Novakovic Dijana Perovic Jelena Carkic Marija Dusanovic Pjevic

Öz

Kaynakça

  • [1] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010; 69(9): 1580-8. https://doi.org/10.1136/ard.2010.138461
  • [2] Schett G, Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol. 2012; 8(11): 656-64. https://doi.org/10.1038/nrrheum.2012.153
  • [3] Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JMW, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poór G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017; 76(6): 960-977. https://doi.org/10.1136/annrheumdis-2016-210715
  • [4] Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, Caporali R, Edwards CJ, Hyrich KL, Pope JE, de Souza S, Stamm TA, Takeuchi T, Verschueren P, Winthrop KL, Balsa A, Bathon JM, Buch MH, Burmester GR, Buttgereit F, Cardiel MH, Chatzidionysiou K, Codreanu C, Cutolo M, den Broeder AA, El Aoufy K, Finckh A, Fonseca JE, Gottenberg JE, Haavardsholm EA, Iagnocco A, Lauper K, Li Z, McInnes IB, Mysler EF, Nash P, Poor G, Ristic GG, Rivellese F, Rubbert-Roth A, Schulze-Koops H, Stoilov N, Strangfeld A, van der Helm-van Mil A, van Duuren E, Vliet Vlieland TPM, Westhovens R, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023; 82(1): 3-18. https://doi.org/10.1136/ard-2022-223356
  • [5] Owen SA, Hider SL, Martin P, Bruce IN, Barton A, Thomson W. Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients. Pharmacogenomics J. 2013; 13(3): 227-34. https://doi.org/10.1038/tpj.2012.7
  • [6] Brown PM, Pratt AG, Isaacs JD. Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nat Rev Rheumatol. 2016; 12(12): 731-742. https://doi.org/10.1038/nrrheum.2016.175
  • [7] Friedman B, Cronstein B. Methotrexate mechanism in treatment of rheumatoid arthritis. Joint Bone Spine. 2019; 86(3): 301-307. https://doi.org/10.1016/j.jbspin.2018.07.004
  • [8] Bierau J, Lindhout M, Bakker JA. Pharmacogenetic significance of inosine triphosphatase. Pharmacogenomics. 2007; 8(9): 1221-8. https://doi.org/10.2217/14622416.8.9.1221
  • [9] Sun R, Huang Y, Zhang H, Liu R. MMP-2, TNF-α and NLRP1 polymorphisms in Chinese patients with ankylosing spondylitis and rheumatoid arthritis. Mol Biol Rep. 2013; 40(11): 6303-8. https://doi.org/10.1007/s11033-013-2743-8
  • [10] Kukkonen MK, Tiili E, Vehmas T, Oksa P, Piirilä P, Hirvonen A. Association of genes of protease-antiprotease balance pathway to lung function and emphysema subtypes. BMC Pulm Med. 2013; 13: 1-10. https://doi.org/10.1186/1471-2466-13-36
  • [11] Mi M, Shi S, Li T, Holz J, Lee YJ, Sheu TJ, Liao Q, Xiao T. TIMP2 deficient mice develop accelerated osteoarthritis via promotion of angiogenesis upon destabilization of the medial meniscus. Biochem Biophys Res Commun. 2012; 423(2): 366-72. https://doi.org/10.1016/j.bbrc.2012.05.132
  • [12] Varani K, Padovan M, Vincenzi F, Targa M, Trotta F, Govoni M, Borea PA. A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res Ther. 2011; 13(6): R197. https://doi.org/10.1186/ar3527
  • [13] Chen Y, Zou K, Sun J, Yang Y, Liu G. Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheumatoid arthritis? A systematic review and meta-analysis. Pharmacogenomics. 2017; 18(2): 175-195. https://doi.org/10.2217/pgs-2016-0158
  • [14] Dervieux T, Wessels JA, van der Straaten T, Penrod N, Moore JH, Guchelaar HJ, Kremer JM. Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis. Pharmacogenet Genomics. 2009; 19(12): 935-44. DOI: 10.1097/FPC.0b013e32833315d1
  • [15] Quaranta S, Thomas F. Pharmacogenetics of anti-cancer drugs: State of the art and implementation–recommendations of the French National Network of Pharmacogenetics. Therapies. 2017; 72(2): 205-15. https://doi.org/10.1016/j.therap.2017.01.005
  • [16] Taylor JC, Bongartz T, Massey J, Mifsud B, Spiliopoulou A, Scott IC, Wang J, Morgan M, Plant D, Colombo M, Orchard P, Twigg S, McInnes IB, Porter D, Freeston JE, Nam JL, Cordell HJ, Isaacs JD, Strathdee JL, Arnett D, de Hair MJH, Tak PP, Aslibekyan S, van Vollenhoven RF, Padyukov L, Bridges SL, Pitzalis C, Cope AP, Verstappen SMM, Emery P, Barnes MR, Agakov F, McKeigue P, Mushiroda T, Kubo M, Weinshilboum R, Barton A, Morgan AW, Barrett JH; MATURA; and PAMERA; Consortia. Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients. Pharmacogenomics J. 2018; 18(4): 528-538. https://doi.org/10.1038/s41397-018-0025-5
  • [17] Relling MV, Klein TE, Gammal RS, Whirl-Carrillo M, Hoffman JM, Caudle KE. The Clinical Pharmacogenetics Implementation Consortium: 10 Years Later. Clin Pharmacol Ther. 2020; 107(1): 171-175. https://doi.org/10.1002/cpt.1651
  • [18] Li P, Tao SS, Zhao MQ, Li J, Wang X, Pan HF, Ye DQ. Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to Rheumatoid Arthritis: A Meta-Analysis. Immunol Invest. 2015; 44(7): 603-15. https://doi.org/10.3109/08820139.2015.1056346
  • [19] Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006; 11: 529-43. https://doi.org/10.2741/1817
  • [20] Combe B, Landewe R, Daien CI, Hua C, Aletaha D, Álvaro-Gracia JM, Bakkers M, Brodin N, Burmester GR, Codreanu C, Conway R, Dougados M, Emery P, Ferraccioli G, Fonseca J, Raza K, Silva-Fernández L, Smolen JS, Skingle D, Szekanecz Z, Kvien TK, van der Helm-van Mil A, van Vollenhoven R. 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis. 2017; 76(6): 948-959. https://doi.org/10.1136/annrheumdis-2016-210602
  • [21] Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial. Arthritis Rheum. 2008; 58(2 Suppl): S126-35. doi: 10.1002/art.23364. PMID: 18240203. https://doi.org/10.1002/art.23364
  • [22] Itoh T, Matsuda H, Tanioka M, Kuwabara K, Itohara S, Suzuki R. The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis J Immunol. 2002; 169(5): 2643-7. https://doi.org/10.4049/jimmunol.169.5.2643
  • [23] Hussein R, Aboukhamis I. Serum matrix metalloproteinase-3 levels monitor the therapeutic efficacy in Syrian patients with rheumatoid arthritis. Heliyon. 2023; 9(3): e14008. https://doi.org/10.1016/j.heliyon.2023.e14008
  • [24] Sabbatini Sabbatini AR, Barbaro NR, de Faria AP, Ritter AMV, Modolo R, Correa NB, Brunelli V, Pinho C, Fontana V, Moreno H. Matrix metalloproteinase-2 -735C/T polymorphism is associated with resistant hypertension in a specialized outpatient clinic in Brazil. Gene. 2017; 620: 23-29. https://doi.org/10.5935/abc.20150060
  • [25] Burgis NE. A disease spectrum for ITPA variation: advances in biochemical and clinical research. J Biomed Sci. 2016; 23(1): 73. https://doi.org/10.1186/s12929-016-0291-y
  • [26] Wessels JA, Kooloos WM, De Jonge R, De Vries-Bouwstra JK, Allaart CF, Linssen A, Collee G, De Sonnaville P, Lindemans J, Huizinga TW, Guchelaar HJ. Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2006; 54(9): 2830-9. https://doi.org/10.1002/art.22032
  • [27] Lee YC, Cui J, Costenbader KH, Shadick NA, Weinblatt ME, Karlson EW. Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate. Rheumatology (Oxford). 2009; 48(6): 613-7. https://doi.org/10.1093/rheumatology/ken513
  • [28] Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Am. 2009;35(4):745-57. Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Rheum Dis Clin North Am. 2009; 35(4): 745-57. https://doi.org/10.1016/j.rdc.2009.10.001
  • [29] Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3): 315-24. https://doi.org/10.1002/art.1780310302
  • [30] Fransen J, Kooloos WM, Wessels JA, Huizinga TW, Guchelaar HJ, van Riel PL, Barrera P. Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure. Pharmacogenomics. 2012; 13(9): 1087-94. https://doi.org/10.2217/pgs.12.83
  • [31] Vejnović D, Milić V, Popović B, Damnjanović T, Maksimović N, Bunjevački V, Krajinović M, Novaković I, Damjanov N, Jekić B. Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotrexate in rheumatoid arthritis patients. Expert Opin Drug Metab Toxicol. 2019; 15(3): 253-257. https://doi.org/10.1080/17425255.2019.1563594
  • [32] Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215. https://doi.org/10.1093/nar/16.3.1215
  • [33] Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005; 21(2): 263-5. https://doi.org/10.1093/bioinformatics/bth457
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Farmakoloji ve Terapötikler
Bölüm Articles
Yazarlar

Milka Grk 0000-0002-7534-9608

Biljana Jekic 0000-0001-6745-5403

Vita Dolzan 0000-0001-6707-6649

Nela Maksimovic 0000-0002-5815-573X

Tatjana Damnjanovic 0000-0003-0479-0620

Milica Rasic 0000-0002-3269-7872

Ivana Novakovic 0000-0003-0202-0673

Dijana Perovic 0000-0003-1077-2373

Jelena Carkic 0000-0002-1014-7589

Marija Dusanovic Pjevic 0000-0002-3564-2623

Yayımlanma Tarihi 28 Haziran 2025
Gönderilme Tarihi 3 Kasım 2023
Kabul Tarihi 20 Aralık 2023
Yayımlandığı Sayı Yıl 2024 Cilt: 28 Sayı: 4

Kaynak Göster

APA Grk, M., Jekic, B., Dolzan, V., Maksimovic, N., vd. (2025). Genetic polymorphisms and Methotrexate response in patients with rheumatoid arthritis. Journal of Research in Pharmacy, 28(4), 1285-1292.
AMA Grk M, Jekic B, Dolzan V, Maksimovic N, Damnjanovic T, Rasic M, Novakovic I, Perovic D, Carkic J, Dusanovic Pjevic M. Genetic polymorphisms and Methotrexate response in patients with rheumatoid arthritis. J. Res. Pharm. Temmuz 2025;28(4):1285-1292.
Chicago Grk, Milka, Biljana Jekic, Vita Dolzan, Nela Maksimovic, Tatjana Damnjanovic, Milica Rasic, Ivana Novakovic, Dijana Perovic, Jelena Carkic, ve Marija Dusanovic Pjevic. “Genetic Polymorphisms and Methotrexate Response in Patients With Rheumatoid Arthritis”. Journal of Research in Pharmacy 28, sy. 4 (Temmuz 2025): 1285-92.
EndNote Grk M, Jekic B, Dolzan V, Maksimovic N, Damnjanovic T, Rasic M, Novakovic I, Perovic D, Carkic J, Dusanovic Pjevic M (01 Temmuz 2025) Genetic polymorphisms and Methotrexate response in patients with rheumatoid arthritis. Journal of Research in Pharmacy 28 4 1285–1292.
IEEE M. Grk, “Genetic polymorphisms and Methotrexate response in patients with rheumatoid arthritis”, J. Res. Pharm., c. 28, sy. 4, ss. 1285–1292, 2025.
ISNAD Grk, Milka vd. “Genetic Polymorphisms and Methotrexate Response in Patients With Rheumatoid Arthritis”. Journal of Research in Pharmacy 28/4 (Temmuz 2025), 1285-1292.
JAMA Grk M, Jekic B, Dolzan V, Maksimovic N, Damnjanovic T, Rasic M, Novakovic I, Perovic D, Carkic J, Dusanovic Pjevic M. Genetic polymorphisms and Methotrexate response in patients with rheumatoid arthritis. J. Res. Pharm. 2025;28:1285–1292.
MLA Grk, Milka vd. “Genetic Polymorphisms and Methotrexate Response in Patients With Rheumatoid Arthritis”. Journal of Research in Pharmacy, c. 28, sy. 4, 2025, ss. 1285-92.
Vancouver Grk M, Jekic B, Dolzan V, Maksimovic N, Damnjanovic T, Rasic M, Novakovic I, Perovic D, Carkic J, Dusanovic Pjevic M. Genetic polymorphisms and Methotrexate response in patients with rheumatoid arthritis. J. Res. Pharm. 2025;28(4):1285-92.